This research will delve into important structure-function relationships of cell membranes through a thorough study of chemical and physical properties of the proteins of the erythrocyte membranes. The objective of this study is to determine the properties of the membrane- associated proteins which are important to their mode of association with the membrane and to relate these properties to the localization of the proteins within the membrane and their biological functions. Membrane proteins will be studied at five levels: whole cell, resealed ghost, isolated membrane, membrane fragment and isolated protein. This multilevel approach is considered essential for an understanding of the integration of each component into the functional structure. A variety of chemical and physical perturbation methods will be used to fragment the membrane into component fractions. Characterization of membranes, fragments and proteins will be performed by chemical modification, protein analytical, spectroscopic and immunochemical methods. Particular attention will be paid to the glycoprotein of the bovine erythrocyte membrane, and efforts will be made to compare its properties with glycoproteins of the bovine milk fat globule membrane. The techniques and concepts developed in these investigations should aid in the expansion of research toward understanding membranes of more complex cells.